The Role of Recombinant LH in Ovarian Stimulation: What's New?

Overview

Journal Reprod Biol Endocrinol

Publisher Biomed Central

Specialties Endocrinology
Reproductive Medicine

Date 2025 Mar 10

PMID 40059197

Authors

Carlo Alviggi

Luigi Vigilante

Federica Cariati

Alessandro Conforti

Peter Humaidan

Affiliations

Soon will be listed here.

Abstract

It is widely recognized that luteinizing hormone (LH) activity is pivotal during folliculogenesis. Nonetheless, the use of LH during ovarian stimulation remains a matter of debate. Indeed, women with good LH function are able to sustain follicle growth and maturation during ovarian stimulation carried out with regimens based on follicle-stimulating hormone (FSH) alone. However, evidence exists that LH activity could be necessary in specific infertile subgroups undergoing assisted reproduction treatment (ART) who are characterized by a functional or constitutive LH deficiency. For instance, women with reduced sensitivity to gonadotropins, also called hypo-responders, usually present with a genetic condition that could impair the function of LH. Furthermore, women of advanced reproductive age present a less functional LH system and consequently reduced androgen production. Reduced ovarian sensitivity and advanced reproductive age represent the main criteria proposed by the POSEIDON group to identify women with impaired prognosis when undergoing ART. Hypogonadotropic hypogonadal women are characterized by undetectable LH levels, thus the addition of LH activity during stimulation is mandatory to achieve satisfactory follicular recruitment. The aim of the present review is to describe the role of recombinant LH in ovarian stimulation, identifying the specific infertile population for whom LH supplementation could improve the outcome of ART.

References

Ferraretti A, La Marca A, Fauser B, Tarlatzis B, Nargund G, Gianaroli L . ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011; 26(7):1616-24. DOI: 10.1093/humrep/der092. View

Shoham Z, Balen A, Patel A, Jacobs H . Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients. Fertil Steril. 1991; 56(6):1048-53. DOI: 10.1016/s0015-0282(16)54715-3. View

Humaidan P, Chin W, Rogoff D, DHooghe T, Longobardi S, Hubbard J . Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders. Hum Reprod. 2017; 32(3):544-555. PMC: 5850777. DOI: 10.1093/humrep/dew360. View

Alviggi C, Mollo A, Clarizia R, De Placido G . Exploiting LH in ovarian stimulation. Reprod Biomed Online. 2006; 12(2):221-33. DOI: 10.1016/s1472-6483(10)60865-6. View

Lehert P, Chin W, Schertz J, DHooghe T, Alviggi C, Humaidan P . Predicting live birth for poor ovarian responders: the PROsPeR concept. Reprod Biomed Online. 2018; 37(1):43-52. DOI: 10.1016/j.rbmo.2018.03.013. View

Kol S . LH Supplementation in Ovarian Stimulation for IVF: The Individual, LH Deficient, Patient Perspective. Gynecol Obstet Invest. 2020; 85(4):307-311. DOI: 10.1159/000509162. View

Liu P, Ji Y, Yuen T, Rendina-Ruedy E, DeMambro V, Dhawan S . Blocking FSH induces thermogenic adipose tissue and reduces body fat. Nature. 2017; 546(7656):107-112. PMC: 5651981. DOI: 10.1038/nature22342. View

Rivero-Muller A, Huhtaniemi I . Genetic variants of gonadotrophins and their receptors: Impact on the diagnosis and management of the infertile patient. Best Pract Res Clin Endocrinol Metab. 2021; 36(1):101596. DOI: 10.1016/j.beem.2021.101596. View

. Recombinant human luteinizing hormone (LH) to support recombinant human follicle-stimulating hormone (FSH)-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. The European Recombinant Human LH Study Group. J Clin Endocrinol Metab. 1998; 83(5):1507-14. DOI: 10.1210/jcem.83.5.4770. View

10.

Filicori M, Cognigni G, Pocognoli P, Ciampaglia W, Bernardi S . Current concepts and novel applications of LH activity in ovarian stimulation. Trends Endocrinol Metab. 2003; 14(6):267-73. DOI: 10.1016/s1043-2760(03)00085-7. View

11.

Casarini L, Riccetti L, De Pascali F, Nicoli A, Tagliavini S, Trenti T . Follicle-stimulating hormone potentiates the steroidogenic activity of chorionic gonadotropin and the anti-apoptotic activity of luteinizing hormone in human granulosa-lutein cells in vitro. Mol Cell Endocrinol. 2015; 422:103-114. DOI: 10.1016/j.mce.2015.12.008. View

12.

Casarini L, Simoni M . Recent advances in understanding gonadotropin signaling. Fac Rev. 2021; 10:41. PMC: 8130412. DOI: 10.12703/r/10-41. View

13.

Sacchi S, Sena P, Esposti C, Lui J, La Marca A . Evidence for expression and functionality of FSH and LH/hCG receptors in human endometrium. J Assist Reprod Genet. 2018; 35(9):1703-1712. PMC: 6133814. DOI: 10.1007/s10815-018-1248-8. View

14.

. Female age-related fertility decline. Committee Opinion No. 589. Fertil Steril. 2014; 101(3):633-4. DOI: 10.1016/j.fertnstert.2013.12.032. View

15.

Zumoff B, Strain G, Miller L, Rosner W . Twenty-four-hour mean plasma testosterone concentration declines with age in normal premenopausal women. J Clin Endocrinol Metab. 1995; 80(4):1429-30. DOI: 10.1210/jcem.80.4.7714119. View

16.

Hugues J . Impact of 'LH activity' supplementation on serum progesterone levels during controlled ovarian stimulation: a systematic review. Hum Reprod. 2011; 27(1):232-43. DOI: 10.1093/humrep/der380. View

17.

Griesinger G, Shapiro D . Luteinizing hormone add-back: is it needed in controlled ovarian stimulation, and if so, when?. J Reprod Med. 2011; 56(7-8):279-300. View

18.

von Wolff M, Kollmann Z, Fluck C, Stute P, Marti U, Weiss B . Gonadotrophin stimulation for in vitro fertilization significantly alters the hormone milieu in follicular fluid: a comparative study between natural cycle IVF and conventional IVF. Hum Reprod. 2014; 29(5):1049-57. DOI: 10.1093/humrep/deu044. View

19.

Garcia-Velasco J, Coelingh Bennink H, Epifanio R, Escudero E, Pellicer A, Simon C . High-dose recombinant LH add-back strategy using high-dose GnRH antagonist is an innovative protocol compared with standard GnRH antagonist. Reprod Biomed Online. 2007; 15(3):280-7. DOI: 10.1016/s1472-6483(10)60340-9. View

20.

Konig T, van der Houwen L, Overbeek A, Hendriks M, Beutler-Beemsterboer S, Kuchenbecker W . Recombinant LH supplementation to a standard GnRH antagonist protocol in women of 35 years or older undergoing IVF/ICSI: a randomized controlled multicentre study. Hum Reprod. 2013; 28(10):2804-12. DOI: 10.1093/humrep/det266. View